Editor’s note: This is the first of a two-part series about eye health. Here, in Part One, Gary Heiting, OD, reviews vitamins and minerals essential to prevent disease and maintain healthy vision. In January, NutraSolutions will present Part Two, which focuses on antioxidant carotenoids such as lutein, zeaxanthin and b-carotene.

According to a recent survey conducted by the Ocular Nutrition Society (a nonprofit organization of eye care providers, nutrition scientists and other professionals dedicated to increasing awareness of the importance of nutrition to eye health), 78% of adults age 45-65 rank vision as the most important of their five senses.

Unfortunately, the same survey revealed that fewer than 50% of respondents were aware of the role key nutrients can play in maintaining healthy eyes and good vision. Worse, a recent study funded by Bausch + Lomb found the diet of many Americans over age 50 doesn’t contain enough of the key nutrients to support eye health. The implications of these shortcomings will likely become even more obvious in the years ahead, as the aging of the U.S. population continues.

It’s estimated the current U.S. population of roughly 315 million will grow to almost 350 million by the year 2025. And, the segment comprising people age 65 and older -- those at greatest risk for age-related eye conditions, such as cataracts and macular degeneration -- will increase by 50% during this period, from 12% of the total population to 18%. That’s 21 million more people in the age group most likely to experience vision loss.

In addition to seriously affecting a person’s quality of life, vision loss also causes financial hardship for many Americans and is a source of significant costs to governmental agencies, employers and private insurers. According to a 2013 report commissioned by Prevent Blindness America, the combined cost of eye disease and vision loss in the U.S. is roughly $139 billion per year, making these problems among the most expensive health issues in the country. More than half of this total cost -- $71.6 billion -- comprises the direct costs to affected individuals and their families.

Many eye care professionals believe improving the American diet and use of specific supplements to fill nutritional gaps can go a long way to reduce these costs and associated quality-of-life issues, especially among individuals at high risk of certain eye problems.

Among the most influential government-sponsored studies in recent years are the “Age-Related Eye Disease Studies” (AREDS and AREDS2). The studies investigated the value of nutraceutical compounds for effectiveness at limiting vision loss from age-related eye problems.

Both studies were sponsored by the National Eye Institute (NEI) and looked specifically into the effect of the use of daily supplements on the risk of age-related macular degeneration (AMD) and cataracts. These conditions are the two leading causes of vision loss in older adults. The supplements researched contained a combination of antioxidant vitamins and other ingredients.

AREDS

AMD is a breakdown of the central portion of the light-sensitive retina -- the inner lining of the back of the eye and the area where photons of light are converted into impulse signals that travel via the optic nerve to vision centers in the brain. AMD gradually destroys the macula, the most sensitive portion of the retina that provides sharp, central vision needed to see and define objects such as road signs, and print in a book or on a computer screen. Currently, there is no cure for macular degeneration.

Cataracts lead to vision loss in a different manner. A cataract is a clouding of the lens of the eye, located directly behind the pupil. Cataracts are very common, affecting approximately 60% of Americans above the age of 60. Cataracts can often be corrected with surgery. More than 1.5 million cataract surgeries are performed in the U.S. each year, making it one of the most frequently performed operations in the country.

Enrollment in the initial AREDS study began in November 1992, and the study was designed to run for a period of 10 years. Results were published in October 2001. A total of 4,757 people, aged 55-80 years, enrolled in the multicenter study. About 90% of participants were followed for a minimum of five years

This first AREDS study evaluated the effect of the use of a daily antioxidant multiple vitamin formula (with or without zinc) on the prevention and/or progression of AMD and cataracts. The supplement used in the study contained 500mg vitamin C, 400 IU vitamin E, 15mg ß-carotene, 80mg zinc (as zinc oxide) and 2mg copper (as cupric oxide).

For the AMD portion of the study, 3,640 participants who had at least early AMD at the time of enrollment were included. The cataract portion of the study was based on 4,629 enrollees, with 128 of the total of 4,757 participants excluded from this portion due to having received cataract surgery on both eyes prior to enrollment.

The AREDS results revealed that patients at high risk of progressive AMD who took the daily supplement had their risk of developing the disease reduced by about 25%. This was in comparison with matched participants who took a placebo. The multivitamin supplement did not provide an apparent benefit among participants who had either no AMD or only early AMD at the time of enrollment, and it did not demonstrate a significant effect on the prevention or progression of cataracts.

Still, because of the apparent protective effect of the supplement against advanced AMD among high-risk individuals, several companies have developed “AREDS formula” eye vitamin supplements.

It is worth noting that other nutritional studies have suggested supplements containing ß-carotene, a vitamin A precursor, could increase the risk of lung cancer among smokers and previous smokers; however, that research is not conclusive. The amounts of ß-carotene used in these studies was beyond the safe upper limit established by the Food and Nutrition Board at the Institute of Medicine and greater than the daily dose used in the AREDS study. However, some health professionals are advising smokers and previous smokers to avoid nutritional supplements containing ß-carotene.

AREDS2

Based on the positive outcome of the original AREDS study, the NEI designed and began a second round of clinical trials in 2006 called AREDS2. The goal was to see if the AREDS-formula supplement could be improved upon to provide even greater eye health benefits.

AREDS2, a five-year study with more than 4,000 participants experiencing varying stages of AMD at the time of enrollment, evaluated the effect of adding lutein (10mg) and zeaxanthin (2mg), and/or omega-3 fatty acids (350mg DHA and 650mg EPA) to the original AREDS formula. These nutrients were chosen because other studies have suggested they have beneficial effects on eye health. AREDS2 also investigated the effect of eliminating ß-carotene and reducing the zinc dosage of the original AREDS formula, to reduce the risk of stomach upset some people experience when taking high doses of zinc.

Results from AREDS2 were published last May. They showed study participants taking the modified AREDS formula that included lutein and zeaxanthin had a 10-25% reduction in the risk of AMD progression. The participants who showed the greatest benefit (i.e., greatest risk reduction of progressive AMD) from lutein and zeaxanthin were those who had the lowest intake of carotenoids from foods in their diet at the time of enrollment in the study. This suggests people who don’t eat a healthful diet, with plenty of carotenoid sources, are those for whom use of daily supplementation with lutein and zeaxanthin could be most important.

Another important finding was that patients who were randomly assigned to take the original AREDS formula containing 15mg ß-carotene had a greater risk of lung cancer during the course of the AREDS2 study, compared with those who were randomly assigned to take the modified formulation without ß-carotene. Most of the participants who developed lung cancer during the study were former smokers.

Many eye care professionals were surprised with one AREDS2 finding: The addition of omega-3 fatty acids to the original AREDS formula did not significantly reduce the risk of AMD progressing to advanced stages.

The study’s authors concluded that adding lutein and zeaxanthin to the original AREDS formula and removing ß-carotene from the supplement could increase its safety and effectiveness in preventing the progression of macular degeneration among people with high risk of vision loss from AMD.

Other Eye Nutrients

In addition to the NEI-sponsored AREDS and AREDS2 studies, many other clinical trials and epidemiological studies have been conducted to investigate the potential benefits of specific nutrients on eye health and the prevention of vision loss from age-related eye diseases. While it’s important to visit the nutraceutical ingredients that have gained the most attention in recent years -- the carotenoids vitamin A, lutein and zeaxanthin -- those will be touched on only briefly here, in order to concentrate on vitamins and minerals less commonly known to help protect the eyes and vision.

Despite the concerns mentioned above regarding the risks of supplements containing high levels of the vitamin A precursor ß-carotene for smokers and previous smokers, vitamin A is essential for eye health. It is specifically crucial for color vision and night vision. Vitamin A also appears to play a critical role in the prevention of xerophthalmia -- dry eyes.

Two forms of vitamin A are available in the human diet: pre-formed vitamin A (retinol and its esterified forms) and provitamin A (carotenoids such as ß-carotene). Good food sources of pre-formed vitamin A include dairy products, fish and meat (especially liver). Good food sources of ß-carotene include carrots, sweet potatoes and spinach.

Lutein and zeaxanthin are yellowish plant pigments that also belong to the class of organic compounds called carotenoids. In nature, lutein and zeaxanthin appear to protect plants from damage caused by high-energy visible light rays (also called HEV or “blue light”). Lutein and zeaxanthin are found in high concentrations in the macula, giving this portion of the retina its yellowish color. Studies suggest these protective pigments reduce the risk of macular degeneration, and there also is some evidence they might reduce the risk of cataracts. Good dietary sources of lutein and zeaxanthin are kale, spinach and collard greens.

Vitamin and Mineral Intervention

Research beyond the AREDS studies suggest vitamin C could help reduce the risk of macular degeneration, especially when taken in combination with other antioxidants. But, vitamin C also appears to help the body form and maintain connective tissue.

While normally associated with collagen and other structural support tissues, collagen also is a key component in the cornea of the eye. Vitamin C displays antioxidant capacity that suggests it could help prevent oxidative changes associated with cataract formation. (Too much vitamin C seems to reverse the antioxidant effects.)

Interestingly, vitamin C’s pro-oxidant effects might not be all bad. In one study, it appeared that the development of reactive oxygen species actually lowered blood pressure. Other studies indicate vitamin C also could help keep small blood vessels healthy, including as those in the retina and on the surface of the eye.

Vitamin E actually is a group of eight related compounds called tocopherols and tocotrienols. They act as powerful antioxidants and help protect cell membranes throughout the body from damage caused by oxygen free radicals. The most active form of vitamin E, a-tocopherol (and its natural form d-a-tocopherol), appears to be more beneficial for the eyes than the synthetic form (dl-a-tocopherol).

While vitamin E demonstrates a role in reducing risk of advanced AMD when used in combination with other antioxidants, other research has found vitamin E may reduce the risk for cataracts, especially when used in combination with other antioxidant vitamins or lutein.

Vitamin E is critical to hundreds of metabolic and cellular functions throughout the body and is required by every cell in the body to maintain the health of cellular membranes. Although there are many good dietary sources of natural vitamin E, including whole-grain cereal, almonds and other nuts, sunflower seeds and avocados, those who do not regularly eat these ingredients might not be getting enough of this vital nutrient.

It is estimated that between one third and two thirds of the population have deficient zinc intakes. In a systematic review by researchers Vishwanathan, Chung and Johnson, published last June in Experimental Eye Research, 10 studies on zinc and eye health were examined. While the evidence for zinc intake and prevention of AMD was deemed inconclusive for zinc on its own, zinc in combination with antioxidants does appear to reduce risk of the disease.

Selenium is another mineral that could be important to eye health. Selenium is unique among trace minerals, in that it has strong antioxidant capacities. It is believed to play a role in both preventing formation of cataracts, as well as AMD. In fact, rat studies showed dietary selenium deficiency induced cataracts. Other rat studies show selenium could help prevent degeneration of retinal capillaries.

It should be mentioned that zinc, selenium and other trace mineral toxicity has been implicated in retinopathy and even hastening cataract development. As always, if these minerals prove to be useful in preventing eye diseases, too much of a good thing can lead to the opposite effect.

Omega-3 Fatty Acids

Though the AREDS2 study failed to show omega-3 fatty acids (EPA and DHA) reduced risk of progressive macular degeneration, other studies suggest omega-3s do indeed offer this benefit. Still other studies show essential fatty acids are crucial to retinal development.

Both omega-3 and omega-6 fatty acids also appear to relieve dry eye problems. In a 2005 study published in Investigative Ophthalmology & Visual Science, oral administration of gamma-linolenic acid (GLA), an omega-6 found in evening primrose oil, blackcurrant seed oil and borage oil, reduced dry eye discomfort and improved the health of the ocular surface in patients with Sjögren’s syndrome, an autoimmune disease that affects production of tears.

Another aspect of omega oils is their ability to help mitigate damage of the endothelial cells of the retina’s vascular system. Failure of these cells is one of the first steps in the development of diabetic retinopathy. Diabetic retinopathy, secondary to uncontrolled hyperglycemia, is one of the leading causes of blindness in Americans.

Results of an animal study published April 2012, in Investigative Ophthalmology & Visual Science, also indicate a beneficial role of omega-3 fatty acids in protecting the retina. Mice with age-related retinal dysfunction were given a diet supplemented with the omega-3 DHA. After six months, they exhibited stabilization of their retinal function, as well as preserved visual function, compared with similar mice fed the same diet without DHA supplementation. (Benefits were not evident until after three months.) The study authors concluded, “Dietary DHA could have broad preventative therapeutic applications [acting on pathologic and normal age-related ocular processes].”Good dietary sources of omega-3s and other potentially beneficial essential fatty acids include salmon and other oily, cold-water fish. Plant sources high in omegas include blackcurrant seed oil; chia seed oil and flaxseed oil; and microalgal sources.

With the aging of the U.S. population, increasing healthcare costs and on-going deficiencies in the diets of many (if not most) Americans, interest in nutraceutical approaches to eye health among consumers is likely to continue to grow in the years ahead. And, eye care professionals have been more proactive lately in counseling patients about potential benefits of nutrition in maintaining healthy eyes and good vision.

 Though more research is needed to identify specific nutrient levels and formulations for optimal ocular protection and visual function, it appears that key nutrients for eye health include a combination of antioxidants (vitamins A, C and E); lutein and zeaxanthin (and perhaps other carotenoids); recommended levels of intake of trace minerals; and omega-3 essential fatty acids.   

Nutritional Amblyopia

-- David Turok, MD

Nutritional amblyopia (also known as toxic optic neuropathy or nutritional optic neuropathy) is a disorder of the optic nerve, particularly involving the maculopapillary bundle of nerve fibers. It causes a centro-cecal scotoma -- loss of central vision from the blind spot to the center of the visual field.

There are numerous causes of this condition, all of which seem to interfere with normal mitochondrial function in the optic nerve and lead to painless, yet progressive, loss of first color vision and, subsequently, central vision.

Smokers and alcoholics were thought to be most at risk for the condition. In fact, the condition used to be termed “tobacco-alcohol amblyopia.” But, B-vitamin deficiencies, particularly B12 and thiamine (B1), are most associated with the disease. Also, other B vitamins, including folate, riboflavin (B2) and niacin (B3), might be involved. As these nutrients often are diminished in alcoholics, this likely was the original association that led to the misnomer.

Other toxic etiologies can cause a similar condition, likely due to their effects on the mitochondria. These include alcohols (methanol, ethylene glycol), certain antibiotics and antimalarial drugs, antitubercular drugs, anti-arrhythmic agents and anticancer drugs, as well as toxicity from heavy metals, such as lead, mercury and thallium, or from gases such as carbon monoxide.

Nutritional amblyopia is unusual in Western civilization, other than with specific groups, such as alcoholics, who are prone to other disease-related pathological conditions resulting from a  vitamin deficiency.

Still, even modern populations can find themselves at risk. For example, in 1993, as a consequence of the collapse of the Soviet Union, the U.S. embargoed Cuba, restricting imports of meat, fish, dairy products, eggs and oil. Since these ingredients are the main dietary sources of vitamin B12, thousands of cases of nutritional amblyopia resulted. Only 38% of the Cuban population had normal thiamine levels. Multivitamins were distributed in May 1993.

By June 1993, there was a significant decline in the incidence of new cases. All told, more than 50,000 people were diagnosed. With a rising trend of vegetarianism/veganism in modern Western society, the possibility of B12 deficiency increases for those who are less than careful in their intake of traditionally animal-sourced nutrients.

It should be noted that in smokers, elevated levels of cyanide are of concern, so B12 replacement is not recommended with the usual cyanocobalamin, but rather with hydroxycobalamin or methylcobalamin, one of the two naturally occurring forms of B12 in humans.

The treatment of toxic amblyopia is, first, removal of the toxin (drugs, cigarettes, alcohol). Additionally, treatment of nutritional amblyopia is a well-balanced diet focusing on green, leafy vegetables and proteins. Vitamin supplementation or fortification, especially of B12, can be useful.

Vision often improves following these interventions, although it might not return fully -- particularly color vision. Improvement is slow, taking weeks to months.

David Turok, MD, has dual board certification in ophthalmology and neurology; he specializes in neuro-ophthalmology, cosmetic surgery and occuloplastic surgery in the northwest suburbs of Chicago. He can be reached at office@drturok.com.